The timing of the first milestone payment for Orum Therapeutics' antibody-degrader conjugate (DAC) pipeline "ORM-6151" is drawing market attention. It is cited as a key variable for the company's goal of turning a profit within the year.
Development of ORM-6151 is proceeding smoothly, with partner Bristol Myers Squibb (BMS) expanding the size of the global phase 1 trial, but interpretations differ on when milestone inflows will actually occur. Orum Therapeutics CEO Lee Sung-joo said at the shareholders' meeting on Mar. that "it is difficult to disclose specific terms due to confidentiality provisions, but given the transaction structure, milestones could come in early."
Orum Therapeutics out-licensed the candidate to BMS in 2023 in a deal worth about 244.2 billion won and received an upfront payment of about 135 billion won at the time. The company had earlier estimated the first development milestone at about 40.3 billion won.
◇ Changed trial design: when is the first milestone
According to the U.S. National Institutes of Health (NIH) clinical registry site (ClinicalTrials.gov), the trial expanded in Jun. last year from two dosing arms to three arms. A triple combination arm of azacitidine and venetoclax was added to the monotherapy and azacitidine double combination arms.
Trial sites have also expanded. Three sites in France and one in Barcelona, Spain, were added. In Apr. this year, one site in Seville, Spain, was also added.
Some suggest that the timing of deriving the "recommended phase 2 dose (RP2D)" could coincide with the milestone payment. RP2D is the stage in early trials where the dose for phase 2 entry is set based on safety and efficacy signals, and it is sometimes used as a criterion for milestone payments in licensing agreements.
Currently, the registry lists the RP2D assessment period as up to two years. Although the ORM-6151 trial began in May 2024, the first patient dosing reportedly took place around Nov. of the same year, leading to speculation in the industry that RP2D could be derived soon.
However, interpretations of the timing differ. A chief scientific officer (CSO) at a domestic pharmaceutical company said, "Depending on how phase 2 is designed, the meaning and timing of RP2D can change," adding, "If a new combination cohort was added, the trial design itself would need to be restructured, which could delay the finalization of RP2D."
By contrast, a clinical lead at a domestic biotech said, "Since evaluation proceeds stepwise from the monotherapy dose to the double combination and then to the triple combination, I don't think increasing the number of arms would, in itself, delay derivation of RP2D."
There is also analysis that more time may be needed as the number of trial sites increases. Another clinical lead at a domestic biotech said, "When participating sites and patient numbers expand, it generally takes more time for enrollment and data accumulation," adding, "In rare cancers, patient recruitment is not easy."
In fact, of the newly added trial sites, two in Spain are recruiting subjects, while the sites in France have not yet begun recruitment. The ORM-6151 trial targets patients with the rare hematologic malignancies relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The type of RP2D is also a key factor. A CEO of a domestic biotech with out-licensing experience said, "RP2D is a concept derived separately for monotherapy, double combination, and triple combination," adding, "Depending on which regimen's RP2D is used as the contractual criterion, the actual timing of the milestone payment may differ."
On this, Orum Therapeutics said, "The increase in trial sites is a positive signal in terms of efficacy," adding, "Given that the primary completion date of phase 1 is expected in Feb. next year, there is a possibility of deriving RP2D within the year."
Regarding the increase in arms, the company said, "Recently, to shorten overall trial timelines, more cases run phase 1 and phase 2 in parallel," adding, "As BMS is leading the trial, we cannot know for sure, but the addition of the triple combination arm to the design could be for that reason."
◇ Earnings gap persists: first-quarter revenue at 0 won
Orum Therapeutics posted consolidated first-quarter revenue of 0 won and an operating loss of 18.1 billion won this year. With research and development expenses continuing, the deficit widened compared with the same period last year (operating loss of 9.6 billion won).
In the securities registration statement submitted earlier for its KOSDAQ listing, the company projected that it would return to profitability this year, recording consolidated annual revenue of 75.2 billion won and operating profit of 31.5 billion won. The assumption reflected the occurrence within the year of the ORM-6151 milestone (about 40.3 billion won) and a milestone related to the U.S. Vertex Pharmaceuticals contract (about 23.5 billion won).
Orum Therapeutics exported its targeted protein degradation (TPD) platform technology to Vertex in 2024. The deal is worth up to 1.3 trillion won, and the company received an upfront payment of about 20.8 billion won at the time.
However, the first milestone related to Vertex (13.5 billion won) that the company reflected in its securities registration statement was not recognized last year, and the follow-on milestone expected this year has not yet occurred.
On this, Orum Therapeutics said it is "focusing on developing follow-up pipelines and generating additional licensing outcomes, even though a short-term return to profit is important." Early this year, the company secured 145 billion won in liquidity by issuing convertible preferred shares (CPS).
The company said, "Including the BMS upfront, we have secured about 280 billion won in cash, so we see no major issues in continuing research and development for the next three to four years," adding, "There are no additional fundraising plans yet."
◇ Reassessing platform value: could this be an opportunity for Orum Therapeutics
Separate from the short-term milestone timing, the expansion of the ORM-6151 trial itself is seen as a signal demonstrating the competitiveness of Orum Therapeutics' DAC platform.
Global big pharma companies are accelerating the race to secure DAC platforms. Last month, U.S. Johnson & Johnson (J&J) acquired Firefly Bio, a local DAC platform specialist biotech, in a deal worth $1 billion (about 1.5 trillion won). That is why there are expectations that clinical results from ORM-6151, developed on Orum Therapeutics' in-house platform, could extend to the value of the company's follow-up pipelines.
The company plans to verify the platform's technological capabilities through ORM-6151 and then proceed with development of follow-up pipelines "ORM-1153" and "ORM-1023."
The company said, "For ORM-1153, we could consider a technology transfer if an offer with appropriate terms comes in even before clinical entry," adding, "We are keeping various deal structures open, including option deals." It added, "For ORM-1023, we plan to finalize the development candidate within the year and select a candidate based on a new payload in the first half of next year."